Post on 22-Jul-2020
Marcos Timón
AEMPS
Interrelación de la legislación de ensayos clínicos con la de organismos
modificados genéticamente
Application of GMO framework
GMOs Medicinal Products: assessment in Europe (MAA)
GMO legislation(deliberate release)
ERA
GMO competent authorities
normally consulted
Q, S & Eassessment
Pharma legislation
Competent authorities
(pharmaceutical)
GMOs Medicinal Products: assessment in Europe (clinical trials)
GMO assessment
GMO legislation
Different competent authorities
Q, S & Eassessment
Pharmaceutical legislation
Competent authorities
(pharmaceutical)
GMOs Medicinal Products: assessment in Europe (clinical trials)
GMO assessment
GMO legislation
Different competent authorities
-Some MS consider deliberate release
(ERA needed)
-Other MS apply contained use
-Other MS case by case
1 2 1
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1 2 1 1 1 1 13 2 1
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8
3 4
87
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ENSAYOS CLÍNICOS AUTORIZADOS
Células MG Virus MG Bacterias MG
1) GMO legislation is not specific for medicinal products-Requested information not appropriate-Review of the applications not in the right context-Different competent authority: possible delays, not always appropriateexpertise available, etc
2) Disparity in processes and timing-Applications before, in parallel or after CT approval
-Interactions with many other entities-Repeated applications with the same ATIMP-Information only in local language
3) The ERA can differ between MS-Different definitions of GMOs-Different legislations applied (e.g. deliberate release vs contained use)
Overview of national requirements
Different approaches across EU (data from 14 MS):
Less than 30 days: 1 MS (but publication of assessment of authorities)
30 days: 9 MS (in 1 MS publication includes assessment of authorities)
6 weeks + 6 weeks waiting period prior to implementation: 1 MS (publication includes draft decision of CA)
60 days: 2 MS
Clinical trials with gene therapy medicinal products: interplay with GMO framework
This presentation only reflects the views of its author and does not necessarily reflect the opinion of the Commission
Objetivos alcanzados
Country sheets
Repository of national requirements published in:
https://ec.europa.eu/health/human-use/advanced-therapies/gmo_investiganional_en
Objetivos alcanzados
Procedimiento simplificado para células modificadas genéticamente con retro o lentivirus (ej. células CAR-T) (incluyendo formulario de solicitud común específico)
Documento de preguntas y respuestas sobre ensayos con medicamentos OMGs ya comercializados
Clinical trials with gene therapy medicinal products: interplay with GMO framework
Are genetically modified cells of human origin to be considered as GMO?
Human beings specifically excluded from definition of GMO.Human cells not able to reproduce in
environment.
Todas las autoridades rechazaron excluirlas
Células modificadas genéticamente
Si no RCV y no partículas infecciosas se puede hacer referencia a ERA estándar
GM-cell Final product
Further processing
Procedimiento simplificado*
*Procedimiento simplificado:
Formulario común completo SNIF No se necesita hacer ERA
Células modificadas genéticamente (mediante retro o lentivirus)
Requisitos imprescindibles:
Demostrar ausencia de RCV y Demostrar ausencia de partículas víricas infecciosas (se puede hacer mediante cálculo teórico: lavados, incubación a 37 °C, etc)
GM-cell Final product
Further processing
Procedimiento simplificado
ERA normal
Células modificadas genéticamente (mediante retro o lentivirus)
GM-cells Good Practice on the assessment of genetically modified cell by
means of retro/lentiviral vectors:
Streamlined approach to facilitate conduct of CTs agreed in 2018 by all MS, except BG, HR, LT, LV, NL, PL, SL, SK, and UK.
Key elements:
Common (streamlined) application form.
Specific ERA: negligible risks to environment.https://ec.europa.eu/health/sites/health/files/files/advtherapies/2018_gmcells_gp_en.pdf
https://ec.europa.eu/health/sites/health/files/files/advtherapies/2018_gmcells_caf_en.pdf
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Open to endorsement by
other MS
Documento de Buenas Prácticas Características de los AAV:
Presentes ampliamente en personas y animales
No patogénicos
Incapaces de replicar por sí mismos (necesitan un virus “helper”)
La mayoría del genoma propio se re-emplaza por el ADN recombinante
Se aplicará ERA específico si:
Ausencia de virus competentes de replicación
El transgén no es peligroso
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Virus Adeno Asociados (AAVs)
Objetivos alcanzados (Octubre 2019)
Procedimiento simplificado para células modificadas genéticamente con retro o lentivirus (ej. células CAR-T) (incluyendo formulario de solicitud común específico)
Documento de preguntas y respuestas sobre ensayos con medicamentos OMGs ya comercializados
Formulario de solicitud común específico para rAAVs
Procedimiento simplificado para rAAVs
Formulario de solicitud común específico para otros virus
Clinical trials with gene therapy medicinal products: interplay with GMO framework